Retrospective Study of the Safety and Efficacy of Anlotinib Combined With Dose-Dense Temozolomide in Patients With Recurrent Glioblastoma

Liao

et al. 2022

Preprint

Purpose IDH1-wt glioblastoma patients with TERTp-mut had the worst prognosis, and no effective management strategy was established after tumor recurrence. The median overall survival (OS) of recurrent GBM patients who only received supportive therapy was approximately 1.0 month. We reported survival outcomes of recurrent glioblastoma (rGBM) treated with anlotinib combined with temozolomide therapy (ACTT), and to explore the management strategy of rGBM. Methods The clinical data of 14 rGBM patients treated with ACTT was collected. Therapeutic efficacy and adverse effects were evaluated in every 2 months of treatment. We also included 16 patients treated with bevacizumab (Bev), 22 with TMZ, 28 with re-operation, 21 with re-irradiation, and 75 with supportive care to make comparison. Kaplan-Meier analysis was used to compare the survival of ACTT group versus other treatment groups. Results Fourteen rGBM patients treated with ACTT were enrolled. After 2-month of ACTT, the overall response and disease control rate were 50.0% and 92.9%, respectively. The 6-months PFS rate was 78.6%, and the 1-year survival rate was 50.0%. The median PFS and OS in ACTT group were 11.0 and 13.0 months, respectively. The median PFS and OS in Bev-group was 4.0 and 8.0 months. The patients treated with ACTT had better PFS than that in Bev-group. And compared to all the others treatment groups, ACTT could prolong survival. Conclusion The treatment regimen of ACTT maybe reliable, safe, and effective for rGBM. The patients can gain survival benefits from ACTT, and prolonged survival were observed compared with other treatment regimens.

Section: Discussionsupporting

confidence: 91%

“…al.' study [23], this may due to our patients were on a 10mg daily dose, while their patients were on a 12mg daily dose. No treatment-related death was presented.…”

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Adverse Eventsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Anlotinib Combined with Temozolomide Therapy for Recurrent Glioblastoma (IDH-wt and TERTp-mut) After Standard Treatment

Liao

et al. 2022

Preprint

Sig Transduct Target Ther

From signalling pathways to targeted therapies: unravelling glioblastoma’s secrets and harnessing two decades of progress

Dewdney,

Jenkins,

Best

et al. 2023

Glioblastoma, a rare, and highly lethal form of brain cancer, poses significant challenges in terms of therapeutic resistance, and poor survival rates for both adult and paediatric patients alike. Despite advancements in brain cancer research driven by a technological revolution, translating our understanding of glioblastoma pathogenesis into improved clinical outcomes remains a critical unmet need. This review emphasises the intricate role of receptor tyrosine kinase signalling pathways, epigenetic mechanisms, and metabolic functions in glioblastoma tumourigenesis and therapeutic resistance. We also discuss the extensive efforts over the past two decades that have explored targeted therapies against these pathways. Emerging therapeutic approaches, such as antibody-toxin conjugates or CAR T cell therapies, offer potential by specifically targeting proteins on the glioblastoma cell surface. Combination strategies incorporating protein-targeted therapy and immune-based therapies demonstrate great promise for future clinical research. Moreover, gaining insights into the role of cell-of-origin in glioblastoma treatment response holds the potential to advance precision medicine approaches. Addressing these challenges is crucial to improving outcomes for glioblastoma patients and moving towards more effective precision therapies.

DNA damage response inhibitors enhance tumour treating fields (TTFields) potency in glioma stem-like cells

Vanderlinden,

Jones,

Myers

et al. 2023

Br J Cancer

Background High-grade gliomas are primary brain cancers with unacceptably low and persistent survival rates of 10–16 months for WHO grade 4 gliomas over the last 40 years, despite surgical resection and DNA-damaging chemo-radiotherapy. More recently, tumour-treating fields therapy (TTFields) has demonstrated modest survival benefit and been clinically approved in several countries. TTFields is thought to mediate anti-cancer activity by primarily disrupting mitosis. However, recent data suggest that TTFields may also attenuate DNA damage repair and replication fork dynamics, providing a potential platform for therapeutic combinations incorporating standard-of-care treatments and targeted DNA damage response inhibitors (DDRi). Methods We have used patient-derived, typically resistant, glioma stem-like cells (GSCs) in combination with the previously validated preclinical Inovitro™ TTFields system together with a number of therapeutic DDRi. Results We show that TTFields robustly activates PARP- and ATR-mediated DNA repair (including PARylation and CHK1 phosphorylation, respectively), whilst combining TTFields with PARP1 or ATR inhibitor treatment leads to significantly reduced clonogenic survival. The potency of each of these strategies is further enhanced by radiation treatment, leading to increased amounts of DNA damage with profound delay in DNA damage resolution. Conclusion To our knowledge, our findings represent the first report of TTFields applied with clinically approved or in-trial DDRi in GSC models and provides a basis for translational studies toward multimodal DDRi/TTFields-based therapeutic strategies for patients with these currently incurable tumours.